An avirulent Vibrio cholerae mutant, called Texas Star-SR (TS-SR), which is unable to produce the A (active or ADP-ribosylating) subunit of the cholera enterotoxin (choleragen) while producing the immunodominant B (binding region or choleragenoid), has been isolated. Tests in rabbits indicate that peroral or intraintestinal inoculation with TS-SR generates highly effective immunity against challenge with virulent cholera vibrios and, to a lesser extent, enterotoxic Escherichia coli and purified cholera enterotoxin (choleragen) and E. coli heat-labile enterotoxin (LT). Further studies are intended to delineate the mechanism(s) involved in this immunity (anti-bacterial, antitoxic, anti-colonization factor, etc.) and to determine optimal dosage regimens, duration and range of immunity. A soluble hemagglutinin (HA) has been isolated from V. cholerae culture supernatants and partially characterized. Further studies are intended to define the role of this factor in adherence to intestinal epithelium and the potential of antibody to it in immunity against cholera. Genetic studies are intended to define the nature of the (genetic) defect in TS-SR and to enable an understanding of cholera toxin synthesis, assembly and transport.